The photochemotherapeutical method means such a chemotherapeutical method which makes use of a photosensitive substance capable of displaying a therapeutic action or medical action for the first time only when said substance is elicited photochemically by being irradiated with light, for example, ultraviolet rays or a beam of laser light, and in which, after the administration of said photosensitive substance, either such part or parts of the tissues of a living body of the patient where the photosensitive substance as administered has been presented and accumulated, or a flow of blood as formed by extracorporeal circulation of the blood containing said photosensitive substance is exposed to irradiation with light or is subjected to any other measure so that the photosensitive substance is elicited photochemically to display its therapeutic or medical action.
Upon the beginning of the development of the photochemotherapy, the photosensitive substances of a first generation, of which a representative is photofrin, were used in the therapeutic treatment of tumors or cancerous tissues. From the viewpoint of clinical application, however, the .[.photosensitvive.]. .Iadd.photosensitive .Iaddend.substance of the first generation are accompanied by their drawback that they are very much slowly metabolized in vivo.
Known photochemotherapeutic methods for treatment of tumor or cancer include such a method wherein such a photosensitiser having no anti-neoplastic activity by itself but having an affinity for tumor or cancer is administered to a patient and the photosensitiser is allowed to concentrate in the tissue of tumor or cancer, followed by irradiating the tumor or cancerous tissue with a laser light so that the tumor or cancerous tissue is treated therapeutically. The photosensitiser used in the above-mentioned method can exert such a mechanism that the photosensitiser, when exposed to the laser light, absorbs the photo-energy of the laser and becomes elicited photochemically and the energy of the elicited photosensitiser can then .[.elicits.]. .Iadd.elicit .Iaddend.the oxygen components present in the tumor or cancer cells to produce activated oxygen, and that the activated oxygen so produced can give damages to the tumor or cancer cells so as to cause necrosis of the tumor or cancer tissue.
For instance, in Japanese patent publication No. 88902/94 and No. 89000/94 as well as European patent publication No. 168832-B1 and U.S. Pat. No. 4,675,338, there is disclosed that diagnosis and therapeutic treatment of tumor or cancereous tissues is conducted with using as a photochemotherapeutic agent such fluorescent tetrapyrrole derivatives or salts thereof which are prepared by condensing an amino-dicarboxylic acid of 4 to 10 carbon atoms, for example, aspartic acid or glutamic acid, via one or more amido linkages with at least one carboxyl group of certain tetrapyrrole compounds bearing a plurality of carboxyl group(s) and side chain(s) of carboxylic acids. There is also disclosed that the aforesaid fluorescent tetrapyrrole derivative, which has concentrated and been accumulated in the tissue of tumor or cancer, can be elicited photochemically by being irradiated with intense light, for example, a laser beam and thereby becomes able to exert its effects of killing the tumor or cancer cells.
Further, it is known that the formation of neovascular blood vessels, namely neovascularization occurs in various ocular tissues in the eyes due to certain pathogenic causes.
Neovascularization of any ocular tissue causes serious visual disturbance. Particularly, choroidal neovascularization which takes place accompanying with age-related macular degeneration is now becoming a primary cause for acquired blindness. In age-related macular degeneration, choroidal neovascularization causes subretinal hemorrhage, exudates and fibrosis, leading to severe visual loss.
Laser photocoagulation has heretofore been used for the therapeutic treatment of choroidal (ocular) neovascularization but is not a perfect method, because it damages overlying sensory retina by propagating heat. Compared with the above method, photochemotherapy using a laser beam is expected to provide a satisfactory therapeutic method for neovascularization, if the neovascular, ocular blood vessels can be selectively targeted by the photochemotherapy with the laser beam.
Sometimes, it is also desired to selectively obstruct or occlude newly-formed vessels other than the above-described ocular .[.Ones.]. .Iadd.ones.Iaddend., for example, those formed in skin tissue or visceral tissue due to a certain pathogenic cause.
An object of the present invention is to provide a new obstruent composition for use in obstructing or occluding photochemotherapeutically and selectively a part or all or some parts of newly-formed vessels formed in the various ocular tissues, as well as newly-formed vessels formed in other tissues in vivo. The other object of the present invention is provide a therapeutic method for photochemotherapeutically obstructing neovascular blood vessels as formed in a patient having the neovascular blood vessels. Another objects of the present invention will be clear from the following descriptions.